miR-489调控PI3K/Akt信号通路促进矽肺诱导小鼠肺纤维化的作用  

miR-489 regulates PI3K/Akt signaling pathway to promote silicosis-induced pulmonary fibrosis in mice

作　　者：邓丽明[1] 周桂芳[2] 梁博萱 梁智萍 赖丽丽[1] 黄蕾蕾[1] DENG Li-ming;ZHOU Gui-fang;LIANG Bo-xuan;LIANG Zhi-ping;LAI Li-li;HUANG Lei-lei(Guangdong Institute of Occupational Disease Control,Guangzhou 510260,Guangdong,CHINA;Department of Cardiology,Nanfang Hospital,Guangzhou 510515,Guangdong CHINA;Southern Medical University,Guangzhou 510515,Guangdong,CHINA)

机构地区：[1]广东省职业病防治院,广东广州510260 [2]南方医院心内科,广东广州510515 [3]南方医科大学,广东广州510515

出　　处：《海南医学》2021年第23期2993-2997,共5页Hainan Medical Journal

基　　金：广东省卫生健康委科研项目(编号:A2018220)。

摘　　要：目的探讨微小核糖核酸(miR)-489调控磷脂酰肌醇三激酶(PI3K)/蛋白激酶B (Akt)信号通路促进矽肺诱导小鼠肺纤维化的作用。方法 SPF级C57BL/6雄性小鼠80只随机分为空白组、模型组、miR-489组和对照组,每组20只。模型组、miR-489组和对照组均通过气管一次灌注SiO2粉尘悬液建立矽肺小鼠模型。染尘操作30 d和45 d后,miR-489组小鼠给予3 nmol的miR-489 agomir尾静脉注射,模型组小鼠给予3 nmol的对照miRNA尾静脉注射,对照组同期尾静脉注射等量生理盐水。染尘操作60 d,取四组小鼠肺组织检测并比较PI3K、Akt蛋白表达水平、miR-489、PI3K、Akt的基因表达差异及肺组织病理纤维化评分。结果空白组小鼠肺组织PI3K、Akt蛋白表达明显低于其他三组,差异有统计学意义(P<0.05);四组小鼠肺组织PI3K、Akt mRNA相对表达量、纤维化评分比较,空白组最低,其次为miR-489组,再次为模型组和对照组,差异均有统计学意义(P<0.05);miR-489组小鼠miR-489的mRNA相对表达量明显高于空白组、模型组和对照组,差异均有统计学意义(P<0.05);HE染色结果显示,模型组和对照组均出现肺泡间隔增厚以及数量众多且大小不一的矽结节,其内可见尘细胞、炎细胞和成纤维细胞,miR-489组出现少量且先相对较小的矽结节,其内含有少量的尘细胞、炎细胞和成纤维细胞。结论 miR-489表达上调有助于矽肺诱导小鼠肺纤维化的防治,抑制PI3K/Akt信号通路可抑制其对小鼠肺纤维化的促进作用。Objective To investigate the effect of microribonucleic acid(miR)-489 in regulating phosphatidylinositol trikinase(PI3 K)/protein kinase B(Akt) signaling pathway to promote silicosis-induced lung fibrosis in mice.Methods A total of 80 SPF C57 BL/6 male mice were randomly divided into blank group,model group,miR-489 group and control group,with 20 mice in each group.Model group,miR-489 group and control group were all perfused with SiO2 dust suspension once through trachea to establish silicosis mouse model.After 30 days and 45 days of dust exposure,the miR-489 group was given 3 nmol of miR-489 agomir by tail vein injection,and the model group was given3 nmol of control miRNA by tail vein injection,and the control group was injected with the same amount of normal saline in the tail vein at the same time.After 60 days of dust exposure,lung tissues of four groups of mice were taken for detection to compare the protein expression of PI3 K and Akt,as well as the gene expression difference of miR-489,PI3 K and Akt,and lung histopathology fibrosis scores.Results The protein expression of PI3 K and Akt in the lung tissue of the blank group was lower than that of the other three groups,and the difference was statistically significant(P<0.05).Comparison of the PI3 K and Akt m RNA relative expression level and fibrosis score in the lung tissues of the four groups showed that the blank group was the lowest,followed by the miR-489 group,then followed by the model group and the control group(P<0.05).The relative expression of miR-489 mRNA in the miR-489 group was higher than that of the blank group,model group and control group,and all differences were statistically significant(P<0.05).HE staining results showed that both the model group and the control group had thickened alveolar septum and numerous silicosis nodules of various sizes,and dust cells,inflammatory cells and fibroblasts were seen in these silicon nodules;there were a few and relatively small silicon nodules in the miR-489 group,which contained a small amount of

关 键 词：小鼠 矽肺 微小核糖核酸-489 PI3K/AKT信号通路 肺纤维化 

分 类 号：R-332[医药卫生]